Guangdong Key Laboratory for Genome Stability & Disease Prevention, International Cancer Center, Department of Pharmacology, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.
College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518055, China.
Int J Mol Sci. 2024 Nov 5;25(22):11873. doi: 10.3390/ijms252211873.
Alzheimer's disease (AD) is a kind of neurodegenerative diseases characterized by beta-amyloid deposition and neurofibrillary tangles and is also the main cause of dementia. According to statistics, the incidence of AD is constantly increasing, bringing a great burden to individuals and society. Nonetheless, there is no cure for AD, and the available drugs are very limited apart from cholinesterase inhibitors and N-Methyl-D-aspartic acid (NMDA) antagonists, which merely alleviate symptoms without delaying the progression of the disease. Therefore, there is an urgent need to develop a medicine that can delay the progression of AD or cure it. In recent years, increasing evidence suggests that metal complexes have the enormous potential to treat AD through inhibiting the aggregation and cytotoxicity of Aβ, interfering with the congregation and hyperphosphorylation of tau, regulating dysfunctional synaptic and unbalanced neurotransmitters, etc. In this review, we summarize the current metal complexes and their mechanisms of action for treating AD, including ruthenium, platinum, zinc, vanadium, copper, magnesium, and other complexes.
阿尔茨海默病(AD)是一种神经退行性疾病,其特征是β-淀粉样蛋白沉积和神经原纤维缠结,也是痴呆症的主要病因。据统计,AD 的发病率不断上升,给个人和社会带来了巨大负担。然而,目前尚无治愈 AD 的方法,除了胆碱酯酶抑制剂和 N-甲基-D-天冬氨酸(NMDA)拮抗剂外,可用的药物非常有限,这些药物只能缓解症状,无法延缓疾病的进展。因此,迫切需要开发一种能够延缓 AD 进展或治愈 AD 的药物。近年来,越来越多的证据表明,金属配合物具有通过抑制 Aβ的聚集和细胞毒性、干扰 tau 的聚集和过度磷酸化、调节功能失调的突触和不平衡的神经递质等途径治疗 AD 的巨大潜力。在本文综述中,我们总结了目前用于治疗 AD 的金属配合物及其作用机制,包括钌、铂、锌、钒、铜、镁等配合物。